EXPRESSION OF SUBUNITS OF THE METALLOENDOPEPTIDASE MEPRIN IN RENAL-CORTEX IN EXPERIMENTAL HYDRONEPHROSIS

Meprin A is a metalloendopeptidase in the proximal tubular epithelium of rodents that is capable of hydrolyzing a great variety of peptides and proteins. The aim of the present investigation was to investigate effects of ureteral ligation on the expression of meprin subunits. Ure teral ligation resulted in marked decreases in the expression of both alpha- and beta-meprin subunits within 12 h of ureteral obstruction. E ven greater downregulation of expression of meprin alpha- and beta-mRN A was noted at 24, 48, and 96 h after ureteral ligation. The greatest decrease in meprin mRNA expression in obstructed kidneys over contrala teral unobstructed control kidneys (CUK) occurred at 24 h postunilater al ureteral obstruction (post-UUO) for the meprin alpha-subunit (20-fo ld decrease compared with controls) and at 48 h for the meprin beta-su bunit (90-fold decrease). On immunolabeling, the intensity for the two meprin subunits at the corticomedullary junction was dramatically dec reased at 24 to 96 h after ureteral ligation in contrast to the CUK sp ecimens. Results of in situ hybridization indicated that the CUK speci mens expressed meprin beta-mRNA at the corticomedullary junction, wher eas the obstructed kidneys exhibited a decrease in mRNA signal for mep rin beta-subunit. There was a steady increase in the interstitial macr ophage number in UUO rat kidneys over the 96 h of evaluation post-UUO. ED-1-positive macrophages were observed almost exclusively in the per itubular cortical interstitial space in a ring-like pattern with a pre ponderance of macrophage clusters around glomeruli. Unexpectedly, afte r reversal of UUO, the interstitial macrophage number remained higher than controls, despite the demonstrable decompression of the renal pel vis and caliceal system. In summary, this investigation demonstrates d ownregulation of meprin alpha and beta within hours of UUO and indicat es a novel tubular response to ureteral obstruction.